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Preparing for a “Pediatric Stroke Alert”
Accepted Manuscript Preparing for a “Pediatric Stroke Alert” Timothy J. Bernard, MD, MSCS, Neil R. Friedman, MBChB, Nicholas V. Stence, MD, William Jones, MD, Rebecca Ichord, MD, Catherine Amlie-Lefond, MD, Michael M. Dowling, MD, Michael J. Rivkin, MD PII:
S0887-8994(15)30074-6
DOI:
10.1016/j.pediatrneurol.2015.10.012
Reference:
PNU 8771
To appear in:
Pediatric Neurology
Received Date: 24 July 2015 Revised Date:
6 October 2015
Accepted Date: 13 October 2015
Please cite this article as: Bernard TJ, Friedman NR, Stence NV, Jones W, Ichord R, Amlie-Lefond C, Dowling MM, Rivkin MJ, Preparing for a “Pediatric Stroke Alert”, Pediatric Neurology (2016), doi: 10.1016/j.pediatrneurol.2015.10.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Preparing for a “Pediatric Stroke Alert”
Timothy J. Bernard, MD, MSCS; Neil R. Friedman, MBChB; Nicholas V. Stence, MD;
Dowling, MD; Michael J. Rivkin, MD
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William Jones, MD; Rebecca Ichord, MD; Catherine Amlie-Lefond, MD; Michael M.
From the Hemophilia and Thrombosis Center (TJB), Department of Neurology (WJ),
Department of Pediatrics (TJB, NSV), Department of Radiology (NVS), University of
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Colorado School of Medicine (TJB, NVS, WJ); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic (NRF); Departments of Neurology and
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Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine of the University of Pennsylvania (RI); Division of Pediatric Neurology, Department of Pediatrics and Neurology, University of Texas Southwestern Medical Center Dallas, Dallas, TX (MMD); Seattle Children's Hospital, Department of Neurology, University of Washington, Seattle (CA-L); and Departments of Neurology, Psychiatry and Radiology, Boston Children’s Hospital and Department of Neurology, Harvard Medical School
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Abstract
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(MJR)
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Childhood arterial ischemic stroke (AIS) is an important cause of morbidity and mortality in children. Hyperacute treatment strategies remain controversial and challenging, especially in the setting of increasingly proven medical and endovascular options in adults. Although national and international pediatric guidelines have given initial direction about acute therapy and management,1;2 pediatric centers have traditionally lacked the infrastructure to triage, diagnose and treat childhood AIS quickly. In addition, these guidelines can become outdated in the current landscape of rapidly changing adult stroke clinical trials. In the past ten years, researchers in the International Pediatric Stroke Study (IPSS) and Thrombolysis in Pediatric Stroke (TIPS) study have initiated
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early strategies for establishing pediatric specific stroke alerts. In this manuscript we discuss the rationale, process and components necessary for establishing a pediatric stroke alert.
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Introduction
Childhood arterial ischemic stroke (AIS) occurs in 1-2 children per 100,000 per year,3
accounting for approximately 1000 childhood strokes in the United States per year. The
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challenges in preparing to accurately diagnose and manage acute childhood AIS are many, including the infrequency of childhood AIS, the lack of data to inform
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management despite the increasing evidence for acute therapies in adults, and the lack of community awareness of stroke occurring in childhood. Although readiness for the management of childhood stroke in the United States and Canada has increased dramatically in the past decade following the formation of the International Pediatric Stroke Study consortium and the subsequent TIPS trial,4;5 preparedness for acute childhood AIS is difficult and treatment decision remain controversial. The purpose of
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this manuscript is to review the current rationale for an acute childhood stroke pathway (or “Stroke Alert/ Code Stroke”), and share our experience with designing a Pediatric Stroke Alert system and pediatric stroke centers.
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Acute interventions for childhood stroke remain highly controversial, with the 2008 American Heart Association Guidelines recommending, “until there are additional published safety and efficacy data, tPA generally is not recommended for children with
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AIS outside a clinical trial (Class III, Level of Evidence C)”.4 However, there was no consensus about the use of tPA in older adolescents who otherwise meet standard adult tPA eligibility criteria.”6 Similarly, CHEST guidelines also recommend “against the use of thrombolysis (tPA) or mechanical thrombectomy outside of specific research protocols (Grade 1C).”2 Despite these cautionary guidelines, tPA is administered in the United States in up to 2% of all children with acute stoke.7 8Indeed, many of the pioneers in the childhood stroke field have published their experience with administration of IV tPA, as well as intra-arterial therapies.9-11 This paradox is likely secondary to several factors,
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including provider comfort with recommending aggressive therapies and increasing evidence about the efficacy of hyperacute systemic and intra-arterial therapies for acute adult stroke. Indeed, the recent evidence demonstrating the effectiveness of endovascular therapies in adult stroke introduces even more uncertainty into these decisions in
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children.12-15 This ambiguity highlights the need for pediatric stroke centers/units to
provide the infrastructure necessary to improve access to acute stroke therapies and trials, provide safe and effective therapies, and improve stroke outcomes.
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If tPA is given to children, it is clear that is should be administered in the setting of a
prepared center that is familiar with adult and child hyperacute guidelines. The early
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IPSS literature underscores this point, as prior to the advent of standardized protocols at most of these centers, children with stroke were sometimes treated outside of standard tPA guidelines. In the original IPSS cohort of 687 children with arterial ischemic stroke presenting from 2003 to 2007, at least four of the 15 children who were administered intravenous (9) or intra-arterial (6) tPA, received treatment outside of standard adult time treatment guidelines,.8 This series also reported that there were no deaths or symptomatic
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intracranial hemorrhage in these children, suggesting tPA in children may be safe,. There is convincing evidence that the establishment of organized adult inpatient units has improved outcomes, including survival and reduced morbidity.16 Advanced preparation for acute childhood AIS is important for comprehensive and standard stroke care and
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enhances a provider’s comfort with acute stroke decision making. Hyperacute therapy
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should only occur in a center which has prepared for this possibility beforehand.
In order to address the lack of evidence about tPA treatment in children with stroke, the IPSS initiated the Thrombolysis in Pediatric Stroke (TIPS) trial in 2012.17 The TIPS trail was a phase 1 multicenter cohort study that examined the safety and dosing of IV tPA in children aged 2 through 17. 18While the trial closed secondary to poor enrollment, the centers participating in the trail reported several important findings from this trial. Centers who participated in the TIPS trial reported a significant increase in self-reported stroke readiness from 6.2 to 8.7 on a 10 point Likert scale (with 10 being completely ready), recording that this change in stroke readiness was secondary to the creation of
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stroke triage protocols, stroke alerts, and stroke order sets.4 Importantly, no child was given tPA outside of standard adult treatment time points, as had been previously reported by the IPSS series from 2003-2007.8 In addition, each center created 24/7 rapidresponse teams possessing neurovascular expertise, a centerpiece to their capabilities to
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consider hyper-acute therapies and initiate standard stroke management. Indeed early treatment decisions surrounding fluid management, treatment of hyperthermia,
antithrombotic management and prevention of hyperglycemia may be more essential in improving childhood AIS outcomes than preparing for tPA administration,19 as the
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majority of children with AIS do not present in time for acute interventions.17;20 As such, an essential piece of “readiness” is to rapidly bring the expertise of the stroke-oriented
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child neurologist (or an adult vascular neurologist) in order to expedite diagnosis and treatment decisions. In addition, when considering stroke as a diagnosis in a child, it is important to provide the right treatment to the right person at the right time. Stroke mimics in pediatric stroke are common and are more often malignant than benign, and can include seizure, metabolic stroke, postictal paralysis, ADEM, tumor, cerebellitis, drug toxicity, idiopathic intracranial hypertension, subdural empyema, AVM, or
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intracranial abscess.21 The operation of an acute stroke pathway therefore offers the prospect for improving timeliness and specificity of a diagnosis and treatment for a wide variety of childhood neurologic emergencies.
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It has also been our experience that increased readiness for childhood stroke brings enhanced visibility to the family of the neurologist’s participation, and that this can
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improve the coping response of families to their child’s illness as well. A lack of readiness can lead to diagnostic and therapeutic uncertainty and/or a lack of initial counseling for families leading to increased familial distress. When families are not counseled accurately about hyper-acute therapies in the acute setting, they are sometimes concerned by perceived inaction, even though childhood stroke recommendations do not endorse intravenous tPA and endovascular therapies, and these therapies are rare in children.2;6 The fact that litigation surrounding adult stroke is much more likely from a lack of action (i.e. not giving tPA) than an adverse reaction to therapy is telling.22 While not giving tPA to a child is always a defensible position given current recommendations,
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explaining this rationale to the family at the time of diagnosis is crucial to building trust with the family.
Finally, readiness for stroke will undoubtedly vary depending on the setting. Some
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tertiary care centers will have stroke alerts with 24/7 in-person consultation by a
neurovascular specialist and urgent MRI capability which support the ability to provide acute intra-arterial therapies and intravenous tPA. Other centers will have less capacity and will undoubtedly rely upon systematic evaluation in the emergency department by
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non-neurologists, with head CT to rule out hemorrhage rather than definitive imaging by MRI, and will appropriately transfer their suspected stroke patient to a center capable of
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urgent management and with expertise in pediatric stroke management. Most centers will create stroke care pathways that fall somewhere in between.
Case 1
A 17-year-old boy was taken to a rural Emergency Department (ED) after awakening
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from a 3-hour nap with right-sided mild/moderate hemiparesis (affecting the arm greater than the leg) and mild aphasia. He was last seen normal 3 hours earlier. He had a mild headache accompanied by nausea, photophobia and photophobia. There was a positive family history of migraine. CT scan of the head was negative. Vascular imaging and
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MRI were not performed. He was admitted overnight for observation for presumed complicated migraine. No one considered or discussed the possibility of stroke or tPA
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treatment with the family, or raised the possibility of a stroke mimic such as acute disseminated encephalomyelitis (ADEM), encephalitis, or seizure and Todd’s paralysis. No further evaluation was undertaken.
The next morning his neurological symptoms had not improved. Upon transfer to a tertiary pediatric care hospital he had an MRI/MRA head that demonstrated a focal cerebral arteriopathy (FCA) and diffusion restriction in his left MCA territory consistent with an acute stroke. His family was understandably upset by the delay in diagnosis, and wondered if tPA treatment could have improved outcome.
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Case 2 A 10-year-old girl was taken to a rural Emergency Department after awakening from a nap with right-sided moderate hemiparesis (arm greater than leg) and mild aphasia. She
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was last seen normal 8 hours earlier. At the ED a stroke is suspected and arrangements were made to transfer her to a pediatric center with a pediatric stroke team and stroke alert system. Prior to transfer a head CT was acquired and yielded normal results. A
maintenance IV was started using normal saline. MRI/MRA at the pediatric tertiary care
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center confirmed a small stroke and distal M1 narrowing, consistent with FCA. The
patient was given aspirin and monitored closely for hyperthermia and hyperglycemia.
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Her mother was informed that her daughter’s condition might worsen overnight due to the M1 arterial narrowing. The family was also educated about the reasons she was not a candidate for tPA. The next day when she sat up she worsened slightly with increased aphasia. An astute resident realized that her symptoms were likely to have been due to hypoperfusion secondary to arterial narrowing, and repositioned her in bed so that she
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was recumbent with resolution of symptoms.
It is unclear if the child in Case 1 would have benefited from tPA or endovascular therapy, as hyperacute therapies in children remain unproven. An adult in this circumstance would have been considered for intervention with intravenous tPA as he
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was less than 4.5 hour from last know normal,23 as well as endovascular therapy as he was also within a six-hour endovascular window.24 Indeed, recently revised AHA
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recommendations suggest, “Endovascular therapy with stent retrievers may be reasonable for some patients <18 years of age with acute ischemic stroke who have demonstrated large vessel occlusion in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset, but the benefits are not established in this age group.’24 In case 2, the establishment of pediatric stroke systems, may have prevented consideration of therapies that are outside of adult clinical time guidelines.
These two cases illustrate different organizational approaches to similar cerebrovascular events in children. Recognition of the possibility of a stroke etiology and need for
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transfer to a pediatric facility organized and experienced for the care of children with acute stroke, a continued search for a diagnosis once transfer was complete, and good communication with the family was essential to patient/family acceptance of the outcome in Case 2. Establishment of protocols and mobilizing all available resources at the rural
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and tertiary care settings provided the resources and education necessary to attain the
higher level of care evident in case 2. As such, it is our opinion that the stroke readiness created by stroke alert systems in Case 2 should become our common goal as pediatric
neurologists during this decade. Even with a stroke protocol in place, there will be times
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that a child with a focal neurological deficit will be initially misdiagnosed or that stroke will not be the first diagnosis ruled-out; however, recognition that acute focal neurologic
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deficit in a child is an emergency, warranting a search for a definitive diagnosis, seems warranted in our current healthcare setting.
Institutional Support and Partnerships
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Establishment of a stroke alert system and pediatric stroke center involves multiple partnerships and participants. Identifying a champion for pediatric stroke who has general knowledge of this disease and specific knowledge of the institutional environment is the first step in establishing collaboration from hospital administration
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and staff. As the establishment of a stroke alert will undoubtedly require resources, enlisting the support of hospital administration is essential. The necessary resources will
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likely vary by center, with tertiary care centers likely needing more infrastructure than primary community-based settings. Indeed, the great majority of the TIPS participants reported receiving hospital support for their stroke program,4 equivalent to adult Primary Stroke Center Criteria. While all of these centers reported the involvement of a dedicated pediatric neurologist, most also reported involvement of a dedicated hematologist (76%), neuroradiologist (76%), neurosurgeon (88%), interventional radiologist (65%), cardiologist (53%), rheumatologist (59%), neuropsychologist (65%) and rehabilitation specialist (65%) with their stroke team.4 Emergency room physicians and adult stroke neurologists can also be important stakeholders in building a collaborative approach and
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comprehensive stroke program. At our centers, we have developed multidisciplinary stroke councils that meet regularly to discuss the quality of our stroke alert procedures, monitor outcomes, and strategize to improve quality and outcomes. As part of this infrastructure, we also have regularly recurring educational activities such as weekly case
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management conferences, lecture series, and annual seminars for key departments at our centers. Educational activities are most effective when they target all major participants and disciplines, including nursing and physicians, and both the front line emergency care providers as well as subspecialty care providers who care for high-risk patients such as
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cardiologists, intensivists and neurosurgeons. Indeed, the educational effort necessary to establish a functional stroke alert system is high, with TIPS centers reporting a mean of
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10 formal lectures related to institutional education of the stroke alert.4 It is important to note that this effort is an ongoing need.
Stroke Alert Preparedness
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Stroke Alert
The stroke alert should include a systematic approach to the identification, triage, evaluation, and management of each child with a focal neurologic deficit or history
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suggestive of stroke. Initial symptoms for stroke in children are similar to adults, allowing for a similar approach to screening. Indeed the FAST criteria (Facial droop, Arm Weakness, Speech Disturbance, Time to Call 911) can identify 4/5 childhood
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strokes.25 While each center can create their own screening tool, the key is to be consistent and include an educational component for your protocol. Most importantly, front line providers in emergency departments, urgent care sites and hospital floors need to be educated and advised on signs of stroke in children. An example triage protocol is found in Figure 1. Once a potential stroke has been identified, a stroke alert can be called via pager, text message or phone call to the on-call stroke neurologist and other team members. In fully resourced tertiary centers, the team may determine that the stroke alert should page simultaneously to all members of a multidisciplinary group, which allows for
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a coordinated team approach that can include the neurologist, imaging team, ICU, nursing, cardiologist, MRI technician, pharmacist and hematologist. In other centers, the stroke alert may go first to a highly selected subset of the team, for example the on-call stroke neurologist, who triages the call and then mobilizes appropriate members of the
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larger team as needed. After the alert, evaluation of stroke systems by the neurologist or delegate should include a PedsNIHSS to document severity of systems.26 As soon as the senior on-call stroke neurologist determines whether stroke is a possibility, they can
advise the front line clinicians as to which diagnostic testing is appropriate and the timing
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of that testing. This may include comprehensive metabolic panel, EKG, PT/INR, PTT, liver functions, ESR, CRP, toxicology screening, pregnancy testing, and chest X-ray.
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This can be streamlined and is an invaluable part of an ED pediatric stroke order set. In addition, simple first-line treatments should be considered including establishing IV access and treating seizures, fever, hypoxia, hyperglyciemia and/or hypoglycemia as appropriate. These steps likewise can be incorporated into order sets.
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Imaging
When the possibility of pediatric stroke is raised, the care pathway requires options for obtaining urgent imaging, and with that comes the appropriate sedation/anesthesia and nursing support staff to safely carry out sedated imaging in an acutely ill child. The
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decision as to what imaging to obtain and how quickly it is necessary becomes part of the initial stroke alert triage process. The advantages and disadvantages of brain CT and/or
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MRI as first line investigation for pediatric stroke are outlined in Table 1. In adult AIS the first-line imaging modality for diagnosis and treatment decision-making is noncontrast CT (NCCT) of the head, optionally followed by head and neck CT angiography (CTA) and, often, brain CT perfusion (CTP).27 NCCT is the traditional first-line modality because it is widely available emergently, simple to perform, requires no pre-scan screening, and is the gold standard to screen for intracranial hemorrhage. The most common reason for an acute focal neurologic deficit in older adults is clearly stroke, thus allowing NCCT to be utilized as the mainstay of radiographic evaluation to quickly differentiate hemorrhagic from ischemic stroke, or rarely demonstrating evidence of an
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alternative diagnosis besides stroke. CTA and CTP may provide additional information, such as the presence of large proximal vascular occlusions and the presence of significant ischemic penumbra, that are important when considering endovascular therapy, either as an adjunct to IV thrombolysis or when the patient is beyond the guideline recommended
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IV thrombolytic window of 4.5 hours from symptom onset (or last known normal). While MRI/MRA is used for first line screening in some adult centers, most do not routinely
employ MRI/MRA for emergent evaluation of AIS due to less emergent availability, the need for pre-scan screening for MRI-incompatible implanted devices and other foreign
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bodies, and greater likelihood that a patient is unable to tolerate MRI. In addition,
although abbreviated scanning, such as limiting the scan to diffusion-weighted imaging
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(DWI) and gradient echo (GRE) or an equivalent, substantially reduces scanning time, preparing the patient for MR scanning and the scanning itself takes more time than CT, especially if MRA is included.
Unlike adult stroke where the pretest probability of ischemic and/or hemorrhagic stroke is high in cases of focal neurological deficit, the pretest probability of stroke in children
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with focal neurological deficit is much lower, making definite confirmation of stroke and/or vessel occlusion imperative in most cases. MRI is therefore a more attractive option in children with stroke-like symptoms.21 In one recent series, stroke was the fourth most common cause of acute childhood focal neurologic deficit, being less common than
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hemiplegic migraine, seizure, and Bell’s palsy.28;29 Finally, children are known to be more sensitive to the effects of radiation, and may have a 2-3 time greater lifetime cancer
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risk than a population exposed at older ages. For this reason, avoidance of radiation exposure from CT is more important in the child than the adult, a particularly important consideration when performing a CTA.
There are two main approaches to emergent, first-line brain MRI in evaluation of childhood acute neurological deficit. The first is a fast examination similar to the abbreviated MRI protocols used in the evaluation of adults with suspected stroke that includes only two or three sequences and may obviate the need for sedation: 1) diffusion weighted imaging (DWI) to evaluate for restricted diffusion in a recognized vascular
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pattern; 2) gradient echo (GRE) or susceptibility weighted imaging (SWI) to evaluate for hemorrhage; and 3) MRA to evaluate for large or medium vessel cerebral arterial abnormalities. The advantages to this approach include speed (the first two sequences can be completed in 3-4 minutes on most MRI platforms, with the MRA adding an additional
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5-7 minutes), no need for contrast, and decreased need for general anesthesia. The main disadvantages are an incomplete evaluation for certain pathologies for which the child
may need to return at a later time, and potential need for anesthesia in smaller children despite reduced scan times. The second approach is to perform a full MRI with and
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without contrast and with head and neck MRA to evaluate for all potential causes of
neurologic deficit. If a neuroradiologist or pediatric stroke neurologist is immediately
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available to monitor the scan, and if the critical AIS sequences are performed first (DWI, GRE/SWI, and MRA), this full exam can be halted early for possible therapeutic intervention if findings typical of AIS are identified after the first three sequences.
Sedation for imaging is a frequent requirement for the evaluation of childhood AIS. In general, children greater than 3 months of age and less than 5 or 6 years of age will
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require general anesthesia to complete a full MRI, with less need for anesthesia in an abbreviated exam without contrast. Some children older than 6 will also require anesthesia to successfully complete MRI due to co-morbid medical conditions, developmental delays or anxiety. Because the duration of CT and CTA is much shorter,
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general anesthesia is less frequently required. Even children 4 years and older can commonly complete a CT examination without the need for sedation. Brain CT scans,
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and especially CTA should only be performed using pediatric imaging protocols given the concerns for radiation exposure.
MRI requires more infrastructure and prior planning to consistently perform emergently, and may be reserved for tertiary care centers. Consistently incorporating MRI into a stroke pathway requires both an MRI technologist and a pediatric anesthesia team to be on call and quickly available 24/7, something that is usually only available at tertiary care centers. CT is more commonly available 24/7 in most hospitals, and decreases the likelihood that anesthesia will be required. Identifying the necessary resources and
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decision-making procedures to access urgent imaging requires advanced behind-thescenes planning and consensus among all involved departments – radiology, anesthesia, nursing, critical care, ED medicine.
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For the reasons outlined above, we recommend the first-line use of MRI in the emergent evaluation of possible childhood AIS in most cases when possible. However, this may only be consistently attainable at tertiary care centers. NCCT (with CTA in selected
cases) is an acceptable alternative to emergently exclude hemorrhage (and evaluate for
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clot) when MRI is not available, and, because routing of patients to the most appropriate destination and pre-arrival notification of interventional radiology teams may
hospital transfer in most cases.
Conclusion
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significantly reduce time-to-treatment. CT should be performed prior to hospital-to-
Correct treatment and care requires the correct diagnosis. As such, in children with focal
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neurologic deficits, stroke and stroke mimics need to be evaluated emergently. When considering treatment options, diverse etiologies for pediatric stroke become important considerations. Assembling a team of specialists with rapid response 24/7 capabilities, most importantly stroke neurologists, is the most critical aspect of creating and maintain a
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stroke care pathway. The importance of this aspect of team-building care delivery cannot be overstated. Vascular neurology is a young and rapidly developing subspecialty which
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places demands on the team members that are more complex and more time-intensive than is the case for almost any other area of neurology. Developing and maintain such staff requires time, money and commitment, and in many cases a paradigm shift by department chiefs and hospital administrators so that due credit and support are provided to those team members, both in terms of clinical effort and academic contribution. Development of standardized stroke protocols and pathways, with evidence-based acute management strategies and supportive care where possible, facilitates the evaluation, management treatment of an acute pediatric stroke. These care protocols need to incorporate the treatment of children with focal neurological deficit throughout their care;
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including awareness of pediatric stroke in the community, pre-hospital EMS alerts, rapid triage through the emergency room, standardized evaluation by treating physicians, and implementation of appropriate neuroimaging. Even when hyper-acute therapies are not appropriate, correct diagnosis, supportive care and prevention of secondary stroke
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recurrence is invaluable for improving outcomes and prognosis. Finally, learning from
the TIPS experience, the success future trails in the hyperacute management of childhood stroke will depend upon a functioning network of stroke centers that are capable of rapid
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recognition and treatment of pediatric stroke,
Early and rapid management and treatment of childhood stroke requires the development
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of 24/7 stroke team with a single-call activation system and involvement of an interdisciplinary team as discussed above. Modeled after the experience from adult stroke centers, pediatric stroke centers will provide the infrastructure necessary to standardize care and evaluation, and improve access to acute stroke therapies and trials, and will improve outcomes for pediatric patients with stroke. In addition, the process of creating a stroke alert procedure will allow the stroke team to discuss and determine local
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approaches for consideration of transfer to a pediatric stroke centers, tPA and endovascular therapies prior to being faced with the clinical scenario. Finally, the establishment of a stroke team allows for a multidisciplinary approach to decision-
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making, which can be invaluable in an emergent situation.
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Acknowledgements
Drs. Bernard and Stence are supported through the ASA/Bugher Foundation Stroke Collaborative Research Center (14BFSC17680001)
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(29) Rivkin MJ, deVeber G, Ichord RN et al. Thrombolysis in pediatric stroke study. Stroke 2015;46:880-885.
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Reference List
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Table 1. Pros and Cons of MRI versus CT in Childhood AIS (Adapted from Wintermark, AJNR 2013)1 Features MRI/MRA CT/CTA Radiation ++ Detection of Acute Ischemia ++ Detection of Hemorrhage ++ ++ Detection of Arterial + ++ Abnormality/Clot Sensitivity and Specificity to ++ Other Diagnoses Need for Sedation + Emergent Availability + ++
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(1) Wintermark M, Sanelli PC, Albers GW et al. Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery. J Am Coll Radiol 2013;10:828-832.
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Figure 1. Example Stroke Alert Guideline: Suspected Childhood Stroke*
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Patient has one or more of the following signs/symptoms of Focal Neurological Deficit: Weakness on one side of body Numbness on one side of the body Weakness on one side of the face Able to understand, but not speak Awake and alert, but “word salad” speech Uncoordinated on one side of body
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Unable to see on one side
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Stroke Alert Initial Evaluation and Management Neurology to bedside to evaluate patient and initiate stroke imaging and/or other treatment as appropriate. Vital signs: Pulse ox, height, weight, temperature, pulse, respiratory rate, and blood pressure, now and Q1 hour. Establish IV access and draw stroke labs EKG NPO Head of bed flat, strict bed rest Normotension: target SBP between 50th%ile and 15% above 95th%ile for age. Treat low blood pressure with normal saline. Consider treatment of malignant HTN to lower by no more than 25% over 24 hours. Normovolemia: NS at maintenance (Warning: Hold IV fluids until mass is ruled out with initial scan) Normal O2: Titrate O2 to maintain SPO2 > 92% Normoglycemia: no glucose in IVF unless hypoglycemic Normothermia: treat all T > 38.3°C with acetaminophen Seizure control: AED for suspected seizure activity
Stroke Alert Criteria: Focal Neurological Deficit Older than 30 days of age Symptoms < 12 hours No history of Todd’s paralysis (first time seizure is not a contraindication)
Does patient meet Stroke Alert criteria?
Yes
Call Stroke Alert!
No
Call for neurology consult
Note: ANY physician may call a Stroke Alert xclusion….
* adapted from Children’s Hospital Colorado Stroke Alert Guideline
S0887-8994(15)30074-6
DOI:
10.1016/j.pediatrneurol.2015.10.012
Reference:
PNU 8771
To appear in:
Pediatric Neurology
Received Date: 24 July 2015 Revised Date:
6 October 2015
Accepted Date: 13 October 2015
Please cite this article as: Bernard TJ, Friedman NR, Stence NV, Jones W, Ichord R, Amlie-Lefond C, Dowling MM, Rivkin MJ, Preparing for a “Pediatric Stroke Alert”, Pediatric Neurology (2016), doi: 10.1016/j.pediatrneurol.2015.10.012. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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Preparing for a “Pediatric Stroke Alert”
Timothy J. Bernard, MD, MSCS; Neil R. Friedman, MBChB; Nicholas V. Stence, MD;
Dowling, MD; Michael J. Rivkin, MD
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William Jones, MD; Rebecca Ichord, MD; Catherine Amlie-Lefond, MD; Michael M.
From the Hemophilia and Thrombosis Center (TJB), Department of Neurology (WJ),
Department of Pediatrics (TJB, NSV), Department of Radiology (NVS), University of
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Colorado School of Medicine (TJB, NVS, WJ); Center for Pediatric Neurology, Neurological Institute, Cleveland Clinic (NRF); Departments of Neurology and
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Pediatrics, Children’s Hospital of Philadelphia, Perelman School of Medicine of the University of Pennsylvania (RI); Division of Pediatric Neurology, Department of Pediatrics and Neurology, University of Texas Southwestern Medical Center Dallas, Dallas, TX (MMD); Seattle Children's Hospital, Department of Neurology, University of Washington, Seattle (CA-L); and Departments of Neurology, Psychiatry and Radiology, Boston Children’s Hospital and Department of Neurology, Harvard Medical School
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Abstract
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(MJR)
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Childhood arterial ischemic stroke (AIS) is an important cause of morbidity and mortality in children. Hyperacute treatment strategies remain controversial and challenging, especially in the setting of increasingly proven medical and endovascular options in adults. Although national and international pediatric guidelines have given initial direction about acute therapy and management,1;2 pediatric centers have traditionally lacked the infrastructure to triage, diagnose and treat childhood AIS quickly. In addition, these guidelines can become outdated in the current landscape of rapidly changing adult stroke clinical trials. In the past ten years, researchers in the International Pediatric Stroke Study (IPSS) and Thrombolysis in Pediatric Stroke (TIPS) study have initiated
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early strategies for establishing pediatric specific stroke alerts. In this manuscript we discuss the rationale, process and components necessary for establishing a pediatric stroke alert.
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Introduction
Childhood arterial ischemic stroke (AIS) occurs in 1-2 children per 100,000 per year,3
accounting for approximately 1000 childhood strokes in the United States per year. The
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challenges in preparing to accurately diagnose and manage acute childhood AIS are many, including the infrequency of childhood AIS, the lack of data to inform
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management despite the increasing evidence for acute therapies in adults, and the lack of community awareness of stroke occurring in childhood. Although readiness for the management of childhood stroke in the United States and Canada has increased dramatically in the past decade following the formation of the International Pediatric Stroke Study consortium and the subsequent TIPS trial,4;5 preparedness for acute childhood AIS is difficult and treatment decision remain controversial. The purpose of
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this manuscript is to review the current rationale for an acute childhood stroke pathway (or “Stroke Alert/ Code Stroke”), and share our experience with designing a Pediatric Stroke Alert system and pediatric stroke centers.
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Acute interventions for childhood stroke remain highly controversial, with the 2008 American Heart Association Guidelines recommending, “until there are additional published safety and efficacy data, tPA generally is not recommended for children with
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AIS outside a clinical trial (Class III, Level of Evidence C)”.4 However, there was no consensus about the use of tPA in older adolescents who otherwise meet standard adult tPA eligibility criteria.”6 Similarly, CHEST guidelines also recommend “against the use of thrombolysis (tPA) or mechanical thrombectomy outside of specific research protocols (Grade 1C).”2 Despite these cautionary guidelines, tPA is administered in the United States in up to 2% of all children with acute stoke.7 8Indeed, many of the pioneers in the childhood stroke field have published their experience with administration of IV tPA, as well as intra-arterial therapies.9-11 This paradox is likely secondary to several factors,
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including provider comfort with recommending aggressive therapies and increasing evidence about the efficacy of hyperacute systemic and intra-arterial therapies for acute adult stroke. Indeed, the recent evidence demonstrating the effectiveness of endovascular therapies in adult stroke introduces even more uncertainty into these decisions in
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children.12-15 This ambiguity highlights the need for pediatric stroke centers/units to
provide the infrastructure necessary to improve access to acute stroke therapies and trials, provide safe and effective therapies, and improve stroke outcomes.
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If tPA is given to children, it is clear that is should be administered in the setting of a
prepared center that is familiar with adult and child hyperacute guidelines. The early
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IPSS literature underscores this point, as prior to the advent of standardized protocols at most of these centers, children with stroke were sometimes treated outside of standard tPA guidelines. In the original IPSS cohort of 687 children with arterial ischemic stroke presenting from 2003 to 2007, at least four of the 15 children who were administered intravenous (9) or intra-arterial (6) tPA, received treatment outside of standard adult time treatment guidelines,.8 This series also reported that there were no deaths or symptomatic
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intracranial hemorrhage in these children, suggesting tPA in children may be safe,. There is convincing evidence that the establishment of organized adult inpatient units has improved outcomes, including survival and reduced morbidity.16 Advanced preparation for acute childhood AIS is important for comprehensive and standard stroke care and
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enhances a provider’s comfort with acute stroke decision making. Hyperacute therapy
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should only occur in a center which has prepared for this possibility beforehand.
In order to address the lack of evidence about tPA treatment in children with stroke, the IPSS initiated the Thrombolysis in Pediatric Stroke (TIPS) trial in 2012.17 The TIPS trail was a phase 1 multicenter cohort study that examined the safety and dosing of IV tPA in children aged 2 through 17. 18While the trial closed secondary to poor enrollment, the centers participating in the trail reported several important findings from this trial. Centers who participated in the TIPS trial reported a significant increase in self-reported stroke readiness from 6.2 to 8.7 on a 10 point Likert scale (with 10 being completely ready), recording that this change in stroke readiness was secondary to the creation of
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stroke triage protocols, stroke alerts, and stroke order sets.4 Importantly, no child was given tPA outside of standard adult treatment time points, as had been previously reported by the IPSS series from 2003-2007.8 In addition, each center created 24/7 rapidresponse teams possessing neurovascular expertise, a centerpiece to their capabilities to
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consider hyper-acute therapies and initiate standard stroke management. Indeed early treatment decisions surrounding fluid management, treatment of hyperthermia,
antithrombotic management and prevention of hyperglycemia may be more essential in improving childhood AIS outcomes than preparing for tPA administration,19 as the
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majority of children with AIS do not present in time for acute interventions.17;20 As such, an essential piece of “readiness” is to rapidly bring the expertise of the stroke-oriented
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child neurologist (or an adult vascular neurologist) in order to expedite diagnosis and treatment decisions. In addition, when considering stroke as a diagnosis in a child, it is important to provide the right treatment to the right person at the right time. Stroke mimics in pediatric stroke are common and are more often malignant than benign, and can include seizure, metabolic stroke, postictal paralysis, ADEM, tumor, cerebellitis, drug toxicity, idiopathic intracranial hypertension, subdural empyema, AVM, or
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intracranial abscess.21 The operation of an acute stroke pathway therefore offers the prospect for improving timeliness and specificity of a diagnosis and treatment for a wide variety of childhood neurologic emergencies.
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It has also been our experience that increased readiness for childhood stroke brings enhanced visibility to the family of the neurologist’s participation, and that this can
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improve the coping response of families to their child’s illness as well. A lack of readiness can lead to diagnostic and therapeutic uncertainty and/or a lack of initial counseling for families leading to increased familial distress. When families are not counseled accurately about hyper-acute therapies in the acute setting, they are sometimes concerned by perceived inaction, even though childhood stroke recommendations do not endorse intravenous tPA and endovascular therapies, and these therapies are rare in children.2;6 The fact that litigation surrounding adult stroke is much more likely from a lack of action (i.e. not giving tPA) than an adverse reaction to therapy is telling.22 While not giving tPA to a child is always a defensible position given current recommendations,
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explaining this rationale to the family at the time of diagnosis is crucial to building trust with the family.
Finally, readiness for stroke will undoubtedly vary depending on the setting. Some
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tertiary care centers will have stroke alerts with 24/7 in-person consultation by a
neurovascular specialist and urgent MRI capability which support the ability to provide acute intra-arterial therapies and intravenous tPA. Other centers will have less capacity and will undoubtedly rely upon systematic evaluation in the emergency department by
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non-neurologists, with head CT to rule out hemorrhage rather than definitive imaging by MRI, and will appropriately transfer their suspected stroke patient to a center capable of
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urgent management and with expertise in pediatric stroke management. Most centers will create stroke care pathways that fall somewhere in between.
Case 1
A 17-year-old boy was taken to a rural Emergency Department (ED) after awakening
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from a 3-hour nap with right-sided mild/moderate hemiparesis (affecting the arm greater than the leg) and mild aphasia. He was last seen normal 3 hours earlier. He had a mild headache accompanied by nausea, photophobia and photophobia. There was a positive family history of migraine. CT scan of the head was negative. Vascular imaging and
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MRI were not performed. He was admitted overnight for observation for presumed complicated migraine. No one considered or discussed the possibility of stroke or tPA
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treatment with the family, or raised the possibility of a stroke mimic such as acute disseminated encephalomyelitis (ADEM), encephalitis, or seizure and Todd’s paralysis. No further evaluation was undertaken.
The next morning his neurological symptoms had not improved. Upon transfer to a tertiary pediatric care hospital he had an MRI/MRA head that demonstrated a focal cerebral arteriopathy (FCA) and diffusion restriction in his left MCA territory consistent with an acute stroke. His family was understandably upset by the delay in diagnosis, and wondered if tPA treatment could have improved outcome.
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Case 2 A 10-year-old girl was taken to a rural Emergency Department after awakening from a nap with right-sided moderate hemiparesis (arm greater than leg) and mild aphasia. She
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was last seen normal 8 hours earlier. At the ED a stroke is suspected and arrangements were made to transfer her to a pediatric center with a pediatric stroke team and stroke alert system. Prior to transfer a head CT was acquired and yielded normal results. A
maintenance IV was started using normal saline. MRI/MRA at the pediatric tertiary care
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center confirmed a small stroke and distal M1 narrowing, consistent with FCA. The
patient was given aspirin and monitored closely for hyperthermia and hyperglycemia.
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Her mother was informed that her daughter’s condition might worsen overnight due to the M1 arterial narrowing. The family was also educated about the reasons she was not a candidate for tPA. The next day when she sat up she worsened slightly with increased aphasia. An astute resident realized that her symptoms were likely to have been due to hypoperfusion secondary to arterial narrowing, and repositioned her in bed so that she
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was recumbent with resolution of symptoms.
It is unclear if the child in Case 1 would have benefited from tPA or endovascular therapy, as hyperacute therapies in children remain unproven. An adult in this circumstance would have been considered for intervention with intravenous tPA as he
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was less than 4.5 hour from last know normal,23 as well as endovascular therapy as he was also within a six-hour endovascular window.24 Indeed, recently revised AHA
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recommendations suggest, “Endovascular therapy with stent retrievers may be reasonable for some patients <18 years of age with acute ischemic stroke who have demonstrated large vessel occlusion in whom treatment can be initiated (groin puncture) within 6 hours of symptom onset, but the benefits are not established in this age group.’24 In case 2, the establishment of pediatric stroke systems, may have prevented consideration of therapies that are outside of adult clinical time guidelines.
These two cases illustrate different organizational approaches to similar cerebrovascular events in children. Recognition of the possibility of a stroke etiology and need for
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transfer to a pediatric facility organized and experienced for the care of children with acute stroke, a continued search for a diagnosis once transfer was complete, and good communication with the family was essential to patient/family acceptance of the outcome in Case 2. Establishment of protocols and mobilizing all available resources at the rural
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and tertiary care settings provided the resources and education necessary to attain the
higher level of care evident in case 2. As such, it is our opinion that the stroke readiness created by stroke alert systems in Case 2 should become our common goal as pediatric
neurologists during this decade. Even with a stroke protocol in place, there will be times
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that a child with a focal neurological deficit will be initially misdiagnosed or that stroke will not be the first diagnosis ruled-out; however, recognition that acute focal neurologic
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deficit in a child is an emergency, warranting a search for a definitive diagnosis, seems warranted in our current healthcare setting.
Institutional Support and Partnerships
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Establishment of a stroke alert system and pediatric stroke center involves multiple partnerships and participants. Identifying a champion for pediatric stroke who has general knowledge of this disease and specific knowledge of the institutional environment is the first step in establishing collaboration from hospital administration
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and staff. As the establishment of a stroke alert will undoubtedly require resources, enlisting the support of hospital administration is essential. The necessary resources will
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likely vary by center, with tertiary care centers likely needing more infrastructure than primary community-based settings. Indeed, the great majority of the TIPS participants reported receiving hospital support for their stroke program,4 equivalent to adult Primary Stroke Center Criteria. While all of these centers reported the involvement of a dedicated pediatric neurologist, most also reported involvement of a dedicated hematologist (76%), neuroradiologist (76%), neurosurgeon (88%), interventional radiologist (65%), cardiologist (53%), rheumatologist (59%), neuropsychologist (65%) and rehabilitation specialist (65%) with their stroke team.4 Emergency room physicians and adult stroke neurologists can also be important stakeholders in building a collaborative approach and
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comprehensive stroke program. At our centers, we have developed multidisciplinary stroke councils that meet regularly to discuss the quality of our stroke alert procedures, monitor outcomes, and strategize to improve quality and outcomes. As part of this infrastructure, we also have regularly recurring educational activities such as weekly case
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management conferences, lecture series, and annual seminars for key departments at our centers. Educational activities are most effective when they target all major participants and disciplines, including nursing and physicians, and both the front line emergency care providers as well as subspecialty care providers who care for high-risk patients such as
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cardiologists, intensivists and neurosurgeons. Indeed, the educational effort necessary to establish a functional stroke alert system is high, with TIPS centers reporting a mean of
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10 formal lectures related to institutional education of the stroke alert.4 It is important to note that this effort is an ongoing need.
Stroke Alert Preparedness
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Stroke Alert
The stroke alert should include a systematic approach to the identification, triage, evaluation, and management of each child with a focal neurologic deficit or history
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suggestive of stroke. Initial symptoms for stroke in children are similar to adults, allowing for a similar approach to screening. Indeed the FAST criteria (Facial droop, Arm Weakness, Speech Disturbance, Time to Call 911) can identify 4/5 childhood
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strokes.25 While each center can create their own screening tool, the key is to be consistent and include an educational component for your protocol. Most importantly, front line providers in emergency departments, urgent care sites and hospital floors need to be educated and advised on signs of stroke in children. An example triage protocol is found in Figure 1. Once a potential stroke has been identified, a stroke alert can be called via pager, text message or phone call to the on-call stroke neurologist and other team members. In fully resourced tertiary centers, the team may determine that the stroke alert should page simultaneously to all members of a multidisciplinary group, which allows for
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a coordinated team approach that can include the neurologist, imaging team, ICU, nursing, cardiologist, MRI technician, pharmacist and hematologist. In other centers, the stroke alert may go first to a highly selected subset of the team, for example the on-call stroke neurologist, who triages the call and then mobilizes appropriate members of the
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larger team as needed. After the alert, evaluation of stroke systems by the neurologist or delegate should include a PedsNIHSS to document severity of systems.26 As soon as the senior on-call stroke neurologist determines whether stroke is a possibility, they can
advise the front line clinicians as to which diagnostic testing is appropriate and the timing
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of that testing. This may include comprehensive metabolic panel, EKG, PT/INR, PTT, liver functions, ESR, CRP, toxicology screening, pregnancy testing, and chest X-ray.
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This can be streamlined and is an invaluable part of an ED pediatric stroke order set. In addition, simple first-line treatments should be considered including establishing IV access and treating seizures, fever, hypoxia, hyperglyciemia and/or hypoglycemia as appropriate. These steps likewise can be incorporated into order sets.
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Imaging
When the possibility of pediatric stroke is raised, the care pathway requires options for obtaining urgent imaging, and with that comes the appropriate sedation/anesthesia and nursing support staff to safely carry out sedated imaging in an acutely ill child. The
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decision as to what imaging to obtain and how quickly it is necessary becomes part of the initial stroke alert triage process. The advantages and disadvantages of brain CT and/or
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MRI as first line investigation for pediatric stroke are outlined in Table 1. In adult AIS the first-line imaging modality for diagnosis and treatment decision-making is noncontrast CT (NCCT) of the head, optionally followed by head and neck CT angiography (CTA) and, often, brain CT perfusion (CTP).27 NCCT is the traditional first-line modality because it is widely available emergently, simple to perform, requires no pre-scan screening, and is the gold standard to screen for intracranial hemorrhage. The most common reason for an acute focal neurologic deficit in older adults is clearly stroke, thus allowing NCCT to be utilized as the mainstay of radiographic evaluation to quickly differentiate hemorrhagic from ischemic stroke, or rarely demonstrating evidence of an
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alternative diagnosis besides stroke. CTA and CTP may provide additional information, such as the presence of large proximal vascular occlusions and the presence of significant ischemic penumbra, that are important when considering endovascular therapy, either as an adjunct to IV thrombolysis or when the patient is beyond the guideline recommended
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IV thrombolytic window of 4.5 hours from symptom onset (or last known normal). While MRI/MRA is used for first line screening in some adult centers, most do not routinely
employ MRI/MRA for emergent evaluation of AIS due to less emergent availability, the need for pre-scan screening for MRI-incompatible implanted devices and other foreign
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bodies, and greater likelihood that a patient is unable to tolerate MRI. In addition,
although abbreviated scanning, such as limiting the scan to diffusion-weighted imaging
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(DWI) and gradient echo (GRE) or an equivalent, substantially reduces scanning time, preparing the patient for MR scanning and the scanning itself takes more time than CT, especially if MRA is included.
Unlike adult stroke where the pretest probability of ischemic and/or hemorrhagic stroke is high in cases of focal neurological deficit, the pretest probability of stroke in children
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with focal neurological deficit is much lower, making definite confirmation of stroke and/or vessel occlusion imperative in most cases. MRI is therefore a more attractive option in children with stroke-like symptoms.21 In one recent series, stroke was the fourth most common cause of acute childhood focal neurologic deficit, being less common than
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hemiplegic migraine, seizure, and Bell’s palsy.28;29 Finally, children are known to be more sensitive to the effects of radiation, and may have a 2-3 time greater lifetime cancer
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risk than a population exposed at older ages. For this reason, avoidance of radiation exposure from CT is more important in the child than the adult, a particularly important consideration when performing a CTA.
There are two main approaches to emergent, first-line brain MRI in evaluation of childhood acute neurological deficit. The first is a fast examination similar to the abbreviated MRI protocols used in the evaluation of adults with suspected stroke that includes only two or three sequences and may obviate the need for sedation: 1) diffusion weighted imaging (DWI) to evaluate for restricted diffusion in a recognized vascular
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pattern; 2) gradient echo (GRE) or susceptibility weighted imaging (SWI) to evaluate for hemorrhage; and 3) MRA to evaluate for large or medium vessel cerebral arterial abnormalities. The advantages to this approach include speed (the first two sequences can be completed in 3-4 minutes on most MRI platforms, with the MRA adding an additional
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5-7 minutes), no need for contrast, and decreased need for general anesthesia. The main disadvantages are an incomplete evaluation for certain pathologies for which the child
may need to return at a later time, and potential need for anesthesia in smaller children despite reduced scan times. The second approach is to perform a full MRI with and
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without contrast and with head and neck MRA to evaluate for all potential causes of
neurologic deficit. If a neuroradiologist or pediatric stroke neurologist is immediately
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available to monitor the scan, and if the critical AIS sequences are performed first (DWI, GRE/SWI, and MRA), this full exam can be halted early for possible therapeutic intervention if findings typical of AIS are identified after the first three sequences.
Sedation for imaging is a frequent requirement for the evaluation of childhood AIS. In general, children greater than 3 months of age and less than 5 or 6 years of age will
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require general anesthesia to complete a full MRI, with less need for anesthesia in an abbreviated exam without contrast. Some children older than 6 will also require anesthesia to successfully complete MRI due to co-morbid medical conditions, developmental delays or anxiety. Because the duration of CT and CTA is much shorter,
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general anesthesia is less frequently required. Even children 4 years and older can commonly complete a CT examination without the need for sedation. Brain CT scans,
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and especially CTA should only be performed using pediatric imaging protocols given the concerns for radiation exposure.
MRI requires more infrastructure and prior planning to consistently perform emergently, and may be reserved for tertiary care centers. Consistently incorporating MRI into a stroke pathway requires both an MRI technologist and a pediatric anesthesia team to be on call and quickly available 24/7, something that is usually only available at tertiary care centers. CT is more commonly available 24/7 in most hospitals, and decreases the likelihood that anesthesia will be required. Identifying the necessary resources and
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decision-making procedures to access urgent imaging requires advanced behind-thescenes planning and consensus among all involved departments – radiology, anesthesia, nursing, critical care, ED medicine.
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For the reasons outlined above, we recommend the first-line use of MRI in the emergent evaluation of possible childhood AIS in most cases when possible. However, this may only be consistently attainable at tertiary care centers. NCCT (with CTA in selected
cases) is an acceptable alternative to emergently exclude hemorrhage (and evaluate for
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clot) when MRI is not available, and, because routing of patients to the most appropriate destination and pre-arrival notification of interventional radiology teams may
hospital transfer in most cases.
Conclusion
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significantly reduce time-to-treatment. CT should be performed prior to hospital-to-
Correct treatment and care requires the correct diagnosis. As such, in children with focal
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neurologic deficits, stroke and stroke mimics need to be evaluated emergently. When considering treatment options, diverse etiologies for pediatric stroke become important considerations. Assembling a team of specialists with rapid response 24/7 capabilities, most importantly stroke neurologists, is the most critical aspect of creating and maintain a
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stroke care pathway. The importance of this aspect of team-building care delivery cannot be overstated. Vascular neurology is a young and rapidly developing subspecialty which
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places demands on the team members that are more complex and more time-intensive than is the case for almost any other area of neurology. Developing and maintain such staff requires time, money and commitment, and in many cases a paradigm shift by department chiefs and hospital administrators so that due credit and support are provided to those team members, both in terms of clinical effort and academic contribution. Development of standardized stroke protocols and pathways, with evidence-based acute management strategies and supportive care where possible, facilitates the evaluation, management treatment of an acute pediatric stroke. These care protocols need to incorporate the treatment of children with focal neurological deficit throughout their care;
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including awareness of pediatric stroke in the community, pre-hospital EMS alerts, rapid triage through the emergency room, standardized evaluation by treating physicians, and implementation of appropriate neuroimaging. Even when hyper-acute therapies are not appropriate, correct diagnosis, supportive care and prevention of secondary stroke
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recurrence is invaluable for improving outcomes and prognosis. Finally, learning from
the TIPS experience, the success future trails in the hyperacute management of childhood stroke will depend upon a functioning network of stroke centers that are capable of rapid
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recognition and treatment of pediatric stroke,
Early and rapid management and treatment of childhood stroke requires the development
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of 24/7 stroke team with a single-call activation system and involvement of an interdisciplinary team as discussed above. Modeled after the experience from adult stroke centers, pediatric stroke centers will provide the infrastructure necessary to standardize care and evaluation, and improve access to acute stroke therapies and trials, and will improve outcomes for pediatric patients with stroke. In addition, the process of creating a stroke alert procedure will allow the stroke team to discuss and determine local
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approaches for consideration of transfer to a pediatric stroke centers, tPA and endovascular therapies prior to being faced with the clinical scenario. Finally, the establishment of a stroke team allows for a multidisciplinary approach to decision-
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making, which can be invaluable in an emergent situation.
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Acknowledgements
Drs. Bernard and Stence are supported through the ASA/Bugher Foundation Stroke Collaborative Research Center (14BFSC17680001)
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(2) Monagle P, Chan AK, Goldenberg NA et al. Antithrombotic therapy in neonates and children: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141:e737S-e801S.
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(14) Saver JL, Goyal M, Bonafe A et al. Stent-Retriever Thrombectomy after Intravenous t-PA vs. t-PA Alone in Stroke. N Engl J Med 2015. (15) Jovin TG, Chamorro A, Cobo E et al. Thrombectomy within 8 Hours after Symptom Onset in Ischemic Stroke. N Engl J Med 2015.
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(16) Govan L, Langhorne P, Weir CJ. Does the prevention of complications explain the survival benefit of organized inpatient (stroke unit) care?: further analysis of a systematic review. Stroke 2007;38:2536-2540.
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(17) Amlie-Lefond C, Chan AK, Kirton A et al. Thrombolysis in acute childhood stroke: design and challenges of the thrombolysis in pediatric stroke clinical trial. Neuroepidemiology 2009;32:279-286. (18) Rivkin MJ, DeVeber G, Ichord RN et al. Thrombolysis in pediatric stroke study. Stroke 2015;46:880-885. (19) Bernard TJ, Goldenberg NA, Armstrong-Wells J, Amlie-Lefond C, Fullerton HJ. Treatment of childhood arterial ischemic stroke. Ann Neurol 2008;63:679696.
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(20) Srinivasan J, Miller SP, Phan TG, Mackay MT. Delayed Recognition of Initial Stroke in Children: Need for Increased Awareness. Pediatrics 2009. (21) Shellhaas RA, Smith SE, O'Tool E, Licht DJ, Ichord RN. Mimics of childhood stroke: characteristics of a prospective cohort. Pediatrics 2006;118:704-709.
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(22) Bhatt A, Safdar A, Chaudhari D et al. Medicolegal considerations with intravenous tissue plasminogen activator in stroke: a systematic review. Stroke Res Treat 2013;2013:562564.
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(23) Jauch EC, Saver JL, Adams HP, Jr. et al. Guidelines for the early management of patients with acute ischemic stroke: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke 2013;44:870-947. (24) Powers WJ, Derdeyn CP, Biller J et al. 2015 AHA/ASA Focused Update of the 2013 Guidelines for the Early Management of Patients With Acute Ischemic Stroke Regarding Endovascular Treatment: A Guideline for Healthcare Professionals From the American Heart Association/American Stroke Association. Stroke 2015.
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(25) Yock-Corrales A, Babl FE, Mosley IT, Mackay MT. Can the FAST and ROSIER adult stroke recognition tools be applied to confirmed childhood arterial ischemic stroke? BMC Pediatr 2011;11:93.
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(26) Ichord RN, Bastian R, Abraham L et al. Interrater reliability of the Pediatric National Institutes of Health Stroke Scale (PedNIHSS) in a multicenter study. Stroke 2011;42:613-617.
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(27) Wintermark M, Sanelli PC, Albers GW et al. Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery. J Am Coll Radiol 2013;10:828832.
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(28) Mackay MT, Chua ZK, Lee M et al. Stroke and nonstroke brain attacks in children. Neurology 2014;82:1434-1440.
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(29) Rivkin MJ, deVeber G, Ichord RN et al. Thrombolysis in pediatric stroke study. Stroke 2015;46:880-885.
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Reference List
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Table 1. Pros and Cons of MRI versus CT in Childhood AIS (Adapted from Wintermark, AJNR 2013)1 Features MRI/MRA CT/CTA Radiation ++ Detection of Acute Ischemia ++ Detection of Hemorrhage ++ ++ Detection of Arterial + ++ Abnormality/Clot Sensitivity and Specificity to ++ Other Diagnoses Need for Sedation + Emergent Availability + ++
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(1) Wintermark M, Sanelli PC, Albers GW et al. Imaging recommendations for acute stroke and transient ischemic attack patients: a joint statement by the American Society of Neuroradiology, the American College of Radiology and the Society of NeuroInterventional Surgery. J Am Coll Radiol 2013;10:828-832.
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Figure 1. Example Stroke Alert Guideline: Suspected Childhood Stroke*
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Patient has one or more of the following signs/symptoms of Focal Neurological Deficit: Weakness on one side of body Numbness on one side of the body Weakness on one side of the face Able to understand, but not speak Awake and alert, but “word salad” speech Uncoordinated on one side of body
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Unable to see on one side
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Stroke Alert Initial Evaluation and Management Neurology to bedside to evaluate patient and initiate stroke imaging and/or other treatment as appropriate. Vital signs: Pulse ox, height, weight, temperature, pulse, respiratory rate, and blood pressure, now and Q1 hour. Establish IV access and draw stroke labs EKG NPO Head of bed flat, strict bed rest Normotension: target SBP between 50th%ile and 15% above 95th%ile for age. Treat low blood pressure with normal saline. Consider treatment of malignant HTN to lower by no more than 25% over 24 hours. Normovolemia: NS at maintenance (Warning: Hold IV fluids until mass is ruled out with initial scan) Normal O2: Titrate O2 to maintain SPO2 > 92% Normoglycemia: no glucose in IVF unless hypoglycemic Normothermia: treat all T > 38.3°C with acetaminophen Seizure control: AED for suspected seizure activity
Stroke Alert Criteria: Focal Neurological Deficit Older than 30 days of age Symptoms < 12 hours No history of Todd’s paralysis (first time seizure is not a contraindication)
Does patient meet Stroke Alert criteria?
Yes
Call Stroke Alert!
No
Call for neurology consult
Note: ANY physician may call a Stroke Alert xclusion….
* adapted from Children’s Hospital Colorado Stroke Alert Guideline